The present patent concerns 4-substituted derivatives of pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine. In addition, the patent concerns the use of compounds, herein described, as agents especially, but not limited, for the therapy of tumours and leukaemia, their use for preparing pharmaceutical compositions, methods for the synthesis of compounds and their intermediates.
Over the past three decades, neoplastic diseases have been the second most common cause of death among western population, and the incidence rates have been increasing over time.1 Meanwhile, if the survival rates of cancer patients are increasing substantially, the incidence rates are still very high. The phenotype shift from the standard to the neoplastic one is a substantially complex biological event, involving many alterations in cell physiology. Among them, transduction factor over expression has a critical role, and one of the most studied and interesting modifications are those involving over expression of Src tyrosine kinase (TK).2 Such TK is the prototype member of the non-receptor Src family of protein tyrosine kinases (PTK).3 Src is activated following engagement of many different classes of cellular receptors and participates as a convergence point in different signalling pathways.4,5 In this regard, Src is a critical component of the signalling cascades initiated by TK-linked receptors, such as the epidermal growth factor receptor (EGFR) and G-protein coupled receptors, and is directly associated with, and may regulate signalling via, the EGFR and HER-2/neu PTK receptor,6,7 both of which are involved in cancer. Finally, Src over expression and activation has been correlated with a large number of growth-regulatory processes where Src participates. The process of activation of Src is mediated by the phosphorylation of the tyrosine 416; on this basis, inhibitors of Src phosphorylation process may halt uncontrolled tumour cell growth and play an important role as new therapeutic agents for the treatment of cancer.